Background: Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Changes in the ubiquitination system in GBM cells can promote uncontrolled tumor growth and reduce the effectiveness of treatments. However, the exact targets and regulatory elements of the ubiquitin–proteasome system involved in GBM are still not well understood. Methods: All data were obtained by using in silico analysis, immunohistochemistry, Western blot, RT-qPCR, gene silencing and proliferation assay. Results: Computational and protein analyses show that aggressive gliomas have higher expression of the RING ligase RNF182, with significantly greater levels in glioblastoma (GBM) than in low-grade gliomas. Elevated RNF182 is strongly associated with GBM growth. Experiments using siRNA to inhibit RNF182 in the human glioblastoma cell line U87MG significantly reduced cell proliferation, suggesting that RNF182 promotes tumor growth and may be a potential therapeutic target. Conclusions: These findings create a connection between the ubiquitin–proteasome system and the unchecked growth observed in GBM, identifying RNF182 as a new marker associated with GBM proliferation and an additional target for GBM treatment.

Background: Recent evidence suggests that the antidepressant vortioxetine (Vx) inhibits the growth of glioblastoma (GBM), the most aggressive primary malignant tumor of the CNS. We used five patient-derived GBM cell lines to confirm the anti-GBM effect of Vx and explore its mechanism(s) of action. Methods: We performed in silico analysis, PCR, TUNEL assay, colony assay, and proliferation assay. Results: Vx potently inhibited GBM cell growth, and showed efficacy at concentrations of 0.1 μM that roughly correspond to therapeutic concentrations of Vx in major depression. Other antidepressants, i.e., fluoxetine and duloxetine, inhibited GBM cell growth only at high concentrations. Computational analysis showed that at least three receptor targets of Vx (5-HT₇, 5-HT_1D, and 5-HT_1B) were expressed at moderate/high levels in GBM. The 5-HT_1B receptor transcript was found in all GBM cell lines and was the only detectable Vx target in three of the five cell lines. Blocking 5-HT_1B with SB224289 abolished the anti-GBM effect of Vx, even in cells expressing other Vx. Conclusions: These findings demonstrate that therapeutic concentrations of Vx inhibit GBM cell proliferation and suggest that this action may be mediated, at least in part, by 5-HT_1B receptor activation.

Background: Glioblastoma (GBM) is the most aggressive primary brain tumor and remains difficult to treat because of its highly invasive behavior and resistance to conventional therapies despite surgery, radiotherapy, and chemotherapy. Sodin 5, a novel type-1 ribosome-inactivating protein (RIP), inhibits protein synthesis and displays cytotoxic activity against several tumor cell types, making it a promising candidate for GBM therapy. Methods: The antitumor activity of sodin 5 was evaluated in the U87MG glioblastoma cell line and patient-derived primary GBM cell lines (CG, ZAR, and NULU). Cell viability, migration, and molecular changes were assessed after treatment. Biological activity was also investigated under different pH conditions. Vimentin and phosphorylated ERK (p-ERK) expression were analyzed to investigate the mechanisms underlying sodin 5 activity. Results: Sodin 5 significantly reduced cell viability in all GBM cell lines. Treatment also inhibited cell migration, accompanied by decreased vimentin expression, suggesting cytoskeletal remodeling and reduced invasive potential. Furthermore, sodin 5 decreased p-ERK levels, indicating modulation of signaling pathways involved in proliferation and motility. The protein retained biological activity under different pH conditions, supporting its potential efficacy in the heterogeneous GBM microenvironment. Conclusions: These findings identify sodin 5 as a promising therapeutic candidate for GBM by targeting multiple processes involved in tumor growth and invasion.